Among the numerous proposed and utilized preparative chromatographic techniques are: (1) high performance liquid chromatography (HPLC) with closed-loop recycling and (2) simulated moving bed (SMB) chromatography. HPLC with closed-loop recycling has been known since at least 1959 (R. S. Porter and J. F. Johnson, Nature, 183, 391 (1959)). In closed-loop recycling, the chromatographic profile, after eluting from the column and passing through the detector, is directed to the suction side of the solvent pump. The profile is then sent through the column again, i.e. it is recycled. This recycling increases the number of theoretical plates available for the separation, because in essence closed-loop recycling simulates the use of a longer column. Thus, resolution is increased after each cycle. Since mixing occurs in the pump, some of the separation that occurred in the column, is destroyed. Therefore, closed-loop recycling is feasible only when the resolution gained each time the profile passes through the column is greater than the loss in resolution due to mixing each time the profile passes through the pump. In practice this means that the volume of the column must be much larger than the volume of the pump. During any cycle in which sufficient resolution has been attained, fractions are collected or shaved from the leading and trailing edges of the chromatographic profile using collection valves or a stand-alone fraction collector. A review article, discussing the use of closed-loop recycling in the separation of enantiomers, has been recently been published (J. Dingenen and J. N. Kinkel, J. Chromatography A, 666, 627 (1994)).
SMB chromatography was invented in the early 1960's by workers at UOP (D. B. Broughton, R. W. Neuzil, J. M. Pharis, C. S. Brearley, Chem. Eng. Progress, 66(9), 70 (1970)). SMB chromatography is a continuous process, in which feed is continuously injected into the interior of the circulating SMB profile; two product streams (extract and raffinate) are continuously collected; and fresh mobile phase is also added continuously. The entire profile travels around the system. For example in an SMB system having a 16 column array, at a particular time the feed is injected between columns 7 and 8; the mobile phase is injected between columns 16 and 1; the raffinate is collected between columns 11 and 12; and the extract is collected between columns 3 and 4. When the profile moves a sufficient distance through the system, all the injection and collection points will be switched simultaneously one column length. For example the feed point will be switched to between columns 9 and 10; the mobile phase point, to between columns 1 and 2; the raffinate point to between columns 12 and 13; and the extract point, to between columns 4 and 5. The switching occurs periodically at the appropriate times. At steady state a mass balance is maintained in which the quantity of each component injected is equal to the quantity of each component collected. At steady state the chromatographic profile remains constant in shape and composition. A further characteristic of SMB chromatography is that there are four flow rates across the profile. It is also important to stress that SMB chromatography is truly continuous: the mobile phase and feed pumps never stop pumping material into the system; the extract and raffinate lines never stop delivering collected purified material.
In preparative HPLC with closed-loop recycling, subsequent injections are made only after all components of the sample have been collected or sent to waste. Thus, in ordinary preprative HPLC with closed-loop recyling (or any other type of batch-mode chromatography), fresh sample is never injected into the inerior of the chromatographic profile.
With simulated moving bed (SMB) chromatography, fresh sample is continuously injected into the interior of the circulating chromatographic profile, and two product streams are continuously collected from either end of the profile. SMB is thus a binary separation process because only two fractions are collected. Injecting into the interior of the profile makes the separation inherently a binary separation process.